The forebrain is the most anterior portion of the central nervous system and gives rises to the telencephalon, diencephalon, and the eyes during development. All derivatives of the forebrain originate from the anterior neural plate. Therefore, mutations in genes that disrupt forebrain development provide a powerful tool for dissecting the mechanisms that regionalize the neural plate, establish fate restrictions, and determine the identities of all its main derivatives. We have demonstrated that the restricted pattern of Six3 expression is of functional relevance as its activity is essential for vertebrate forebrain, lens and retina development. The goal of this proposal is to continue with the systematic identification and characterization of the functional roles of Six3 during forebrain and visual system development as a tool to help us unravel the cellular and molecular mechanisms participating in the genesis of these structures. During the last few years we have generated an invaluable collection of animal models and molecular tools that are a great asset in the accomplishment of the proposed goals. To this end, we propose to continue using Six3 as an entry point to better characterize its functional role in the development of different brain structures and retina differentiation and lamination. [unreadable] [unreadable] [unreadable]